Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
Artikel i vetenskaplig tidskrift, 2006

PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.

Statistical

Female

Antibodies

Data Interpretation

Treatment Outcome

Dose Fractionation

therapeutic use

secondary

Mice

Astatine

radiotherapy

Mice

Nude

therapeutic use

therapeutic use

Radiation Dosage

Ovarian Neoplasms

Inbred BALB C

Mice

methods

pathology

Radiopharmaceuticals

Monoclonal

Animals

Radioimmunotherapy

Författare

Jörgen Elgqvist

Göteborgs universitet

Håkan Andersson

Göteborgs universitet

Peter Bernhardt

Göteborgs universitet

Tom Bäck

Göteborgs universitet

Ingela Claesson

Göteborgs universitet

Ragnar Hultborn

Göteborgs universitet

Holger Jensen

Bengt R Johansson

Göteborgs universitet

Sture Lindegren

Göteborgs universitet

Marita Olsson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Stig Palm

Göteborgs universitet

Elisabet Warnhammar Finnborg

Göteborgs universitet

Lars Jacobsson

Göteborgs universitet

International journal of radiation oncology, biology, physics

1879-355X (ISSN)

Vol. 66 1228-37

Ämneskategorier

Cell- och molekylärbiologi

DOI

10.1016/j.ijrobp.2006.07.003

PubMed

17145538